C-reactive protein (CRP) is an acute phase protein in human that increases as much as several hundred-fold during acute pathological conditions. We have previously shown that natural killer (NK) cells have low levels of CRP on their surface since removal of the surface CRP (S-CRP) positive cell subpopulations with anti-CRP and complement (C) eliminates most NK activity. If cells are incubated with high concentrations of anti-CRP in the absence of C, effectors are not killed but no longer function. This implies that the S-CRP is involved in NK-mediated killing. We have recently biotinylated anti-CRP so that less anti-CRP can be used in the presence of avidin to effectively eliminate NK function. Several monoclonal anti-CRP antibodies also have been tested and we have determined that none of the monoclonal antibodies will singly remove NK activity in the absence of C; however, preliminary experiments indicate that at least one combination of monoclonal antibodies may eliminate NK function. These antibodies and heterologous antibodies have been used in a single cell assay to determine if the antibodies block conjugate formation or killing. These assays have been successfully performed but the data concerning the role of CRP is, as yet, too preliminary to report. In summary, CRP is on the NK cell and it appears to be required for NK function; more sensitive and specific reagents have been developed for use in its detection and studies have been initiated to determine if it is involved in recognition or killing. These studies will lead to a better understanding of the NK cell that is involved in the immune surveillance of tumor cells.